Safety and Efficacy of VB10.16 and Pembrolizumab in Patients With Head-Neck Squamous Cell Carcinoma

• Status: Recruiting
• Trial end date: 2028-01-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a multi-center study in patients with un-resectable Recurrent or Metastatic HPV16-positive Head and Neck Squamous Cell Carcinoma (HNSCC). The trial is designed to investigate VB10.16, an investigational therapeutic DNA vaccine in combination with another medicine, pembrolizumab, which is the standard of care for patients with previously untreated metastatic or resectable recurrent PD-L1 positive HNSCC. The study is divided in 2 parts: a phase 1, dose escalation part, testing 3 different doses of VB10.16 in combination with a standard fixed dose of pembrolizumab. The goal of this part is to evaluate the safety and tolerability of the combined treatment and to decide on the dose of VB10.16 to be used in the second part of the trial. In the second part of the trial, a phase 2a, dose expansion part, participants will receive either the highest safe dose of VB10.16 from part 1 or the 3 mg dose both in combination with pembrolizumab. The dose given to each participant will be decided in random.

The trial is designed to define the optimal dose of VB10.16 in combination with pembrolizumab for future clinical studies based on the safety, tolerability and anti-tumor effect data generated.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Nykode Therapeutics ASA
• Collaborator: Merck Sharp & Dohme LLC
• Treatments: Pembrolizumab

Criteria

Inclusion Criteria:

GENERAL REQUIREMENTS

1. ≥18 years of age (or as per national legal age of trial consent, whichever is higher) at date of signing the informed consent form (ICF)

2. Histologically or cytologically confirmed R/M HNSCC considered incurable by local therapy and eligible for monotherapy with pembrolizumab

3. HPV16 positivity of R/M HNSCC confirmed by designated central laboratory

4. PD-L1 positivity (CPS ≥1)

5. Must provide a tumor tissue sample collected prior to VB10.16 treatment initiation for baseline tumor microenvironment analyses

6. Primary tumor location in the oropharynx, oral cavity, hypopharynx, or larynx

7. At least 1 measurable lesion per RECIST 1.1

ORGAN FUNCTION

Overall function:

8. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1

Hematological function:

9. Platelets 100 - 400 × 10^9/L (100,000 - 400,000/µL)

10. Neutrophils (absolute neutrophil count [ANC]) ≥1.5 × 10^9/L (1,500/µL)

11. Hemoglobin ≥5.6 mmol/L (9.0 g/dL)

Hepatic and hemostatic function:

12. Bilirubin (BILI), total ≤1.5 × upper limit of normal (ULN) (except Gilbert syndrome, then direct BILI ≤2 × ULN)

13. Aspartate transaminase (AST) ≤ 2.5 × ULN

14. Alanine transaminase (ALT) ≤ 2.5 × ULN

15. Alkaline phosphatase ≤ 2.5 × ULN

16. International normalized ratio (INR) ≤1.5 × ULN

Renal function:

17. Estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73 m^2 using the Cockroft-Gault formula

OTHER TRIAL REQUIREMENTS

18. Female patients of childbearing potential: negative serum pregnancy test (≤72 hours)

19. Female patients of childbearing potential and male patients must agree to use highly effective contraception, and male patients must refrain from sperm donation throughout the trial (14 days prior to initiation of treatment for oral contraception), and for at least 120 days (according to the latest country-specific pembrolizumab label) after the last dose of pembrolizumab and up to 6 months after the last dose of VB10.16, whichever comes last

20. Patients capable of giving informed consent must provide signed and dated written informed consent prior to initiation of any study-related procedures.

Exclusion Criteria:

HNSCC DISEASE

1. Has disease that is suitable for local therapy with curative intent

2. Has progressive disease ≤6 months after completion of curatively intended systemic treatment for locoregionally advanced R/M HNSCC

3. Primary tumor site of the nasopharynx (any histology)

4. Rapidly progressing disease (e.g., tumor bleeding, uncontrolled tumor pain) in the opinion of the investigator

PRIOR, CONCURRENT, OR FUTURE INTERVENTIONS

5. Has received prior radiotherapy within 2 weeks of start of trial treatment or has had a history of radiation pneumonitis

6. Any prior investigational or approved systemic antineoplastic drug or invasive medical device (including ICIs), either as monotherapy or as part of a combination regimen administered in the R/M HNSCC setting

7. Prior solid organ or tissue transplantation (except corneal transplant)

8. Prior autologous or allogeneic hematopoietic stem cell transplantation (HSCT)

9. Prior chimeric antigen receptor T (CAR-T) cell therapy

10. Prior therapy with a monoclonal or bispecific antibody or antibody fragment (or other molecule with similar mechanism of action) that engages T-cells

11. Has received a live or live-attenuated vaccine within 30 days prior to the first dose of trial intervention

12. Administration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine within 30 days prior to VB10.16 treatment start

13. Prior administration with a therapeutic HPV16 vaccine

14. Patients receiving systemic immunosuppression with immunosuppressive agents such as cyclosporine, azathioprine, methotrexate, or tumor necrosis factor alpha (TNF α) blockers for any concurrent condition

15. Chronic administration of systemic corticosteroids: prednisone >10 mg daily (or dose equivalent) or an average cumulative dose of >140 mg prednisone (or dose equivalent) within the last 14 consecutive days prior to VB10.16 treatment start

16. Administration of G-CSF/GM-CSF or transfusions with red blood cells, platelets, or plasma components ≤2 weeks prior to VB10.16 treatment start

17. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137)

18. Has received prior surgery or prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to treatment

19. Any planned major surgery

PRIOR OR CONCURRENT MORBIDITY

Malignancy:

20. Past or current malignancy other than inclusion diagnosis, except for:

• Cervical carcinoma, stage 1B or less

• Noninvasive basal cell or squamous cell skin carcinoma

• Noninvasive, superficial bladder cancer

• Prostate cancer with a current prostate-specific antigen level <0.1 ng/mL

• Any curable cancer with a complete response of >2 years' duration

Hepatic and hemostatic function:

21. Any current bleeding disorder, active bleeding, or bleeding diathesis

Cardiovascular function:

22. Symptomatic congestive heart failure (Grade III or IV as classified by the New York Heart Association), unstable angina pectoris, or cardiac arrhythmia

23. History of myocardial infarction ≤ 6 months prior to planned VB10.16 treatment start

24. Uncontrolled hypertension (systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg), despite optimal medical management

25. Any other significant cardiac disease(s) that, in the opinion of the investigator, is/are clinically significant and/or unacceptable

Pulmonary function:

26. Has a history of (non-infectious) pneumonitis / interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease

Immune system and infectious diseases:

27. Primary immunodeficiency, other immunosuppressive disorder, and/or other causes of immunosuppression

28. Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed

29. Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by a local health authority

30. Has a known history of Hepatitis B (defined as HBsAg reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection

31. Any active, acute, or chronic infection that is uncontrolled and/or requires systemic treatment

32. Known allergies, sensitivity, or intolerance to drug excipients, or aminoglycosides (especially kanamycin).

Central nervous system (CNS) function:

33. Any history of intracerebral arteriovenous malformations, cerebral aneurysm, or stroke

34. Has known active CNS metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during trial screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of trial treatment

35. New (≤6 months), progressive and/or symptomatic brain metastases

OTHER

36. Is currently participating in or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of trial treatment

37. Has a history or current evidence of any condition, therapy, or laboratory abnormality, or other circumstance that might confound the results of the trial or interfere with the patient's participation for the full duration of the trial, such that it is not in the best interest of the patient to participate, in the opinion of the treating investigator

38. Has a known psychiatric or substance abuse disorder that would interfere with the patient's ability to cooperate with the requirements of the trial

39. Has a concomitant medical condition requiring receipt of a therapeutic anticoagulant that, in the opinion of the treating physician, would contraindicate administration of VB10.16 and tumor biopsies

40. Female patients who are pregnant or breastfeeding